Some processes are known for the production of optically active 2-cyclopropane carboxamide derivatives, optically active 2-aryl cyclopropylamine derivatives, and optically active 2-arylcyclopropane-1-carboxylate ester derivatives.
Examples of processes for the production of optically active 2-arylcyclopropane carboxamide derivatives are:
(i) A process wherein excess thionyl chloride is reacted with optically active 2-phenylcyclopropane carboxylic acid in benzene solvent to form corresponding acid chloride, and after concentrating down excess thionyl chloride and benzene under reduced pressure, the acid chloride is isolated and purified by distillation, and, by causing ammonia water to act on this, 2-phenylcyclopropane carboxamide is obtained (J. Am. Chem. Soc. Vol. 109, p. 2311 (1987), Journal of Medicinal Chemistry Vol. 20, p. 771 (1977)); and
(ii) A Process to obtain optically active 3-aryl-2-dimethylcyclopropane-1-carboxamide by causing ammonia water to act on the corresponding acid chloride formed by reacting thionyl chloride with optically active 3-aryl-2-dimethylcyclopropane-1-carboxylic acid (J. Org. Chem. Vol. 68, p. 621 (2003)).
Examples of processes for the production of optically active 2-aryl cyclopropylamine derivatives are:
(iii) A process wherein chlorocarbonic acid ethyl ester is reacted with 2-aryl cyclopropane carboxylic acid to form mixed acid anhydride, and by causing to act sodium azide on this, corresponding acid azide is formed, and 2-aryl cyclopropylamine is obtained by Curtius rearrangement with this (Journal of Medicinal Chemistry Vol. 20, p. 771 (1977), WO01/92263); and
(iv) A process to obtain corresponding 2,2-dimethyl cyclopropylamine by causing chlorine, bromine or sodium hypochlorite to act on the optically active 2,2-dimethylcyclopropane-1-carboxamide in the presence of base (Kokoku 5-3865);
Examples of a process for the production of optically active 2-arylcyclopropane carboxylate ester derivatives are:
(v) A process to obtain optically active cyclopropanecarboxylic acid derivative by cyclopropanation after deriving into optically active ester or amide via several steps using benzaldehyde derivative as the starting material (WO01/92263); and
(vi) A process to obtain optically active 2-dihydrofuranyl cyclopropanecarboxylate derivative by reacting phosphonoacetic acid ester derivative with optically active dihydrobenzofuranyl ethylene oxide derivative in the presence of base (Organic Process Research & Development, vol 6, p. 618 (2002)).
Examples of a process to produce optically active 2-aryl cyclopropylamine derivatives from optically active 2-aryl cyclopropanecarboxylic acid are:
(vii) A process wherein benzaldehydes is used as the starting material and derived into optically active ester or amide via several steps, and thereafter optically active 2-aryl cyclopropane carboxylate ester is obtained by cyclopropanation. This optically active carboxylic acid derivative is formed into acid azide, and optically active 2-aryl cyclopropylamine derivative is produced by Curtius rearrangement (WO01/92263).
In the process for the production of optically active 2-arylcyclopropane carboxamides referred to in (i) above, only the process to produce 2-phenylcyclopropane carboxamide from 2-phenylcyclopropane carboxylic acid is described and a process for production for 2-(disubstituted aryl)cyclopropane carboxamide derivative is not disclosed. Moreover, in the process (ii) above, there is mentioned the process for production only of 2,2-dimethyl-3-phenylcyclopropane carboxamide and 2,2-dimethyl-3-isopropylidene cyclopropane carboxamide, and a process for production of 2-(disubstituted aryl) cyclopropane carboxamide derivative is not disclosed.
Secondly, in a process for the production of optically active 2-aryl cyclopropylamine derivative, optically active 2-aryl cyclopropylamine derivative is produced by Curtius rearrangement from optically active 2-arylcyclopropane carboxylic acid in the aforesaid process (iii), however, it is not suitable for a commercial preparation method from the viewpoint of safety because it is via an acid azide intermediate having explosive properties. Moreover, in the process (iv), optically active amine is produced from the optically active carboxamide by a Hofmann rearrangement. However, it is not suitable for a commercial preparation method from the viewpoint of economy because yield is low when the reaction is carried out using the sodium hypochlorite. Moreover, as for the aforesaid process (iv), only the process to produce optically active 2,2-dimethyl cyclopropylamine from optically active 2,2-dimethylcyclopropane carboxamide is mentioned, and a process for production of 2-(disubstituted aryl)cyclopropane carboxamide derivative is not disclosed.
Thirdly, in a process for the production of optically active 2-arylcyclopropane carboxylate ester derivative, in the aforesaid process (v), optically active 3,4-difluorophenyl cyclopropanecarboxylic derivative is obtained by cyclopropanation after converting 3,4-difluoro benzaldehyde starting material into optically active ester or amide via several steps. However, it is not commercially suitable from the viewpoint of productivity and economy. For example, the starting material is expensive, the stereoselectivity is insufficient in the cyclopropanation and also there are many numbers of steps. Moreover, in process (vi), only an example of preparing optically active dihydrofuranyl cyclopropanecarboxylate ester from optically active dihydrobenzofuranyl ethylene oxide is mentioned. It is not a process for the production of general optical activity 2-arylcyclopropane carboxylate ester.
Fourthly, a process to produce optically active 2-aryl cyclopropylamine derivative from optically active 2-arylcyclopropane carboxylate ester derivative using (vii) is not commercially viable from a safety standpoint because the acid azide intermediate has expulsion properties. Also, purification is essential due to insufficient stereoselectivity during the cyclopropanation, making this process unsuitable for commercial preparation because of poor productivity.
Thus, the processes outlined are unsuitable for commercial production. There is a need for a commercial process which addresses areas such as safety, economy, productivity and the like.